Generally, overweight people having accumulated visceral fat are more likely to have diabetes and vascular diseases such as hypertension and arteriosclerosis. Thus, it is considered that visceral fat accumulation is a common base for triggering the development of pathologic conditions. In the development of the pathologic conditions by the fat accumulation, proteins made by adipocytes are considered to be involved, and it has been shown that a gene which is expressed into a fat tissue has a high frequency of secretory protein genes, among which a gene of a biologically active substance such as complement and growth factor is included. Such a substance (also referred to as adipocytokine) essentially plays an important role in the metabolism of adipocyte itself, but is considered to have an adverse effect on the overall metabolism of a subject by causing excessive secretion or conversely insufficient secretion during fat accumulation. For example, Shimomura et al. have shown that plasminogen activator inhibitor-1 (PAI-1), an important regulation factor of fibrinolytic system, is expressed in a remarkably increased amount especially in visceral fat if fat accumulation occurs, and thereby increasing its blood concentration, which can be one of the factors for vascular complication [Shimomura, I. et al., “Nature medicine (Nat. Med.)”, (USA), Vol. 2 (No. 7), pp. 800-803 (1996)]. It has been also shown that a gene which is specifically and expressed with high frequency in fat tissues, adipose most abundant gene transcript-1 encoding collagen-like protein (adiponectin), exists abundantly in human blood and has the action of strongly inhibiting the growth of vascular smooth muscle cell, but conversely has such a low level in blood of overweight people that it leads to the development of vascular diseases [Arita, Y. et al., “Biochemical and Biophysical Research Communications (Biochem. Biophys. Res. Commun.)”, (USA), Vol. 257 (No. 1), pp. 79-83 (1999)].
It has also been suggested that adipocytes perform fat degradation as well as synthesis of large amount of fats, and release fatty acid and glycerol into the blood, but aquaporin adipose which is a membrane protein and cloned by Kuriyama et al., is likely to serve as glycerol channel molecule in the adipocytes [Kishida, K. et al., “Journal of Biological Chemistry (J. Biol. Chem.)”, (USA), Vol. 275 (No. 27), pp. 20896-20902 (2000)].
As described above, the adipocytes secret various biologically active substances (i.e., ligand), and also express a membrane protein (i.e., receptor) on the cell surface. Thus, by regulating the expression or biological activities of such secretory or membrane protein, the development of a novel method of preventing and/or treating obesity, diabetes and vascular disease (e.g., arteriosclerosis) can be expected.
Conventionally, a substance which inhibits the binding of a biologically active substance (i.e., ligand) to a cell surface receptor and a substance which is bound and induces signal transduction like the biologically active substance (i.e., ligand) have been used as medicines regulating biological functions as a specific antagonist or agonist for such receptors. Accordingly, as described above, the discovery of a novel membrane receptor protein and a ligand molecule thereof (e.g., secretory protein) which are important in the expression in the living body and also can be a target for drug development, and cloning of its gene (e.g. cDNA), can be very important means for discovering a specific ligand, agonist, and antagonist of the novel receptor protein, or a specific receptor of the novel secretory protein.
However, all of the proteins secreted from adipocyte or expressed on the cell surface have not been discovered, and many of the secretory or membrane proteins are unknown at present, and thus search for a novel ligand or a receptor and elucidation of its function are strongly desired.
Therefore, an object of the present invention is to identify a novel secretory or membrane protein gene which is specifically and highly expressed in adipocyte, which can be a useful tool for developing prophylactic and/or therapeutic agents for obesity, diabetes, arteriosclerosis, etc., or a useful diagnosis marker for such diseases. Further, another object of the present invention is to provide a recombinant vector containing the novel gene, a transformant having the recombinant vector, a method of producing the secretory or membrane protein by cultivating the transformant, an antibody for the secretory or membrane protein, its partial peptide or a salt thereof, a compound for changing the amount of expression of the secretory or membrane protein, a method of determining a biological substance having specific affinity for the secretory or membrane protein, a method of screening a compound (antagonist and agonist) or a salt thereof for changing the binding property between the biological substance having specific affinity and the secretory or membrane protein, a kit for the screening, a compound for changing the binding property between the biological substance having specific affinity and the secretory or membrane protein (antagonist and agonist) or a salt thereof, which is obtained by using the method of screening or the screening kit, and a medicine comprising the compound for changing the binding property between the biological substance having specific affinity and the secretory or membrane protein (antagonist and agonist) or the compound for changing the expression amount of the secretory or membrane protein or a salt thereof, etc.